Abstract Rationale Prevention of exacerbations is a major goal for asthma and COPD management and therefore, an important outcome in clinical development. However, exacerbation event rates are low, often resulting in lengthy, large and costly trials. CompEx Asthma and COPDCompEx have recently been proposed as novel endpoints of disease worsenings that include both exacerbations and worsening episodes captured by daily measures of asthma or COPD symptoms and lung function. CompEx events occur more frequently than exacerbation events. Therefore, treatment effect can be observed earlier with CompEx than with exacerbations alone. We hypothesized that capturing CompEx events as they occur in real-time, offers opportunities for further clinical trial acceleration as compared to standard CompEx evaluations. Methods Real-time CompEx uses automated data collection where the CompEx pipeline ingests patient-reported outcomes, device measurements, and electronic case report form data into a single location as soon as it is available. Configurable mappings and transformations are applied in near real-time, aligning incoming data with study-specific requirements and preparing it for downstream analysis. The CompEx algorithm runs daily on the harmonized data to calculate composite endpoints for exacerbations in asthma and COPD, supporting standardized and reproducible event definitions across studies. Processed data is automatically visualized in interactive dashboards, providing study teams and statisticians with low-latency access to key metrics such as the number of CompEx events, subject randomization, and treatment completion rates. Examples of trials implementing real-time CompEx are the ongoing FLASH asthma Phase 2 trial (NCT05251259), and the recently completed CRESCENDO COPD Phase 2A trial (NCT05492877). Results All data flows and dashboard access are managed through secure, compliant (GxP) cloud infrastructure, with role-based access controls to ensure data privacy and integrity. This end-to-end automation enables rapid, data-driven decision-making for clinical studies, reducing latency between data collection and actionable insights. The real-time assessment of COPDCompEx has delivered a further reduction of clinical development timelines for the CRESCENDO trial by 6%, associated to a further reduction in development costs by 7% as compared to the standard COPDCompEx endpoint. Real-time assessment of CompEx Asthma is still ongoing in the FLASH trial. Conclusions Real-time monitoring of the CompEx endpoints allows for flexible trial sample size adjustments with potential to end trials earlier as demonstrated here for COPDCompEx. The dashboard is customizable and not only opens the door to event-driven trial opportunities to accelerate clinical trial development further, but also opens a realm of cost-effective opportunities for better management of exacerbations. This abstract is funded by: AstraZeneca and Evinova
Silva et al. (Fri,) studied this question.